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Record W4410748172 · doi:10.1002/cbic.202500220

Chemical Switching: A Concept Inspired by Strategies from Biocatalysis and Organocatalysis

2025· review· en· W4410748172 on OpenAlexfundno aff
Torkild Visnes, Kaixin Zhou, Aurino M. Kemas, Dominic J. Campopiano, Volker M. Lauschke, Maurice Michel

Bibliographic record

VenueChemBioChem · 2025
Typereview
Languageen
FieldBiochemistry, Genetics and Molecular Biology
TopicDNA Repair Mechanisms
Canadian institutionsnot available
FundersInnovative Medicines InitiativeEuropean Federation of Pharmaceutical Industries and AssociationsOntario Institute for Cancer ResearchMcGill UniversityDiamond Light SourceKungliga Tekniska Högskolan
KeywordsBiocatalysisOrganocatalysisFunction (biology)Protein functionSynthetic biologyDNABiochemical engineeringReactive intermediateChemistryNanotechnologyComputational biologyBiologyBiochemistryReaction mechanismEnantioselective synthesisMaterials scienceCatalysisGeneticsEngineering

Abstract

fetched live from OpenAlex

In this perspective the character of aldehyde functional groups is outlined as central intermediates in DNA repair. As highly reactive entities, aldehydes exist in limited quantities and in contextualized scenarios only and are commonly masked as a Schiff base. Recent advances reveal that principles of organic chemistry can modulate the enzymatic cleavage of Schiff bases, a process termed chemical switching. This approach not only enhances the production of canonical DNA repair products, bolstering cellular function, but also generates novel reaction intermediates, potentially rewiring cellular pathways. However, such rewiring could increase the complexity and toxicity of DNA repair intermediates, influencing therapeutic outcomes. To shape novel classes of therapeutics, an exploitation of these fine-tuned reaction principles requires expertise of enzymologists and scientists skilled in bio- and organocatalysis. Here, the current state of the art is outlined in chemically switching enzymatic function in cells with focus on DNA repair, highlighting challenges of this new type of protein modulation and discussing possible solutions. This paints a picture of the chemical switching concept as an emerging playing field with exciting translational prospects.

Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.

How this classification was reachedexpand

Full frame distilled prediction

Teacher imitation

Not calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.

metaresearch head score (Codex)0.000
metaresearch head score (Gemma)0.000
Version: codex-gemma-dda1882f352aValidation status: machine_predicted_unvalidated
Candidate categoriesMeta-epidemiology (narrow)
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Bench or experimental · Consensus signal: Bench or experimental
GenreCandidate signal: Review · Consensus signal: Review
Teacher disagreement score0.454
Threshold uncertainty score0.999

Codex and Gemma teacher scores by category

CategoryCodexGemma
Metaresearch0.0000.000
Meta-epidemiology (narrow)0.0010.001
Meta-epidemiology (broad)0.0020.001
Bibliometrics0.0000.000
Science and technology studies0.0000.000
Scholarly communication0.0000.000
Open science0.0010.001
Research integrity0.0010.000
Insufficient payload (model declined to judge)0.0000.000

Machine scores (provisional)

The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.

Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.

Opus teacher head0.009
GPT teacher head0.268
Teacher spread0.259 · how far apart the two teachers sit on this one work
Validation statusscore_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it

Classification

machine, unvalidated

Machine predicted; a candidate call from one teacher head, not a consensus.

Study designBench or experimental
Domainnot available
GenreReview

How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".

Quick stats

Citations4
Published2025
Admission routes1
Has abstractyes

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